Isolation of Chlamydia trachomatis from men with urethritis: relative value of one vs. two swabs and influence of concomitant gonococcal infection.
Two successive urethral swabs were used to obtain specimens for culture of Neisseria gonorrhoeae and Chlamydia trachomatis from 136 heterosexual men with urethritis. The first swab was used to culture N. gonorrhoeae and then C. trachomatis; the second was used to culture C. trachomatis only. C. trachomatis cultures from the second swab were positive more often (30 of 31 pairs) than were cultures from the first swab (22 of 31 pairs) (P less than .05). In addition, cultures from swab 2 had greater numbers of inclusions per coverslip more frequently (23 of 31 pairs) than did cultures from the first swab (six of 31 pairs) (P = .003). Numbers of chlamydial inclusions per coverslip were lower in specimens positive for both C. trachomatis and N. gonorrhoeae than in specimens positive for C. trachomatis only (P less than .02). In addition, the presence of N. gonorrhoeae in a specimen adversely affected the quality of the McCoy cell monolayer. In 17 of 21 instances of monolayer toxicity, cultures for N. gonorrhoeae were positive (P less than .01). These results demonstrate that when specimens from men with urethritis are cultured for N. gonorrhoeae and C. trachomatis, use of a second swab will improve rates of recovery of C. trachomatis. Material present in specimens that contain N. gonorrhoeae may adversely affect rates of isolation of C. trachomatis.


Identification of a strawberry NPR-like gene involved in negative regulation of the salicylic acid-mediated defense pathway.
Hormonal modulation plays a central role in triggering various resistant responses to biotic and abiotic stresses in plants. In cultivated strawberry (Fragaria x ananassa), the salicylic acid (SA)-dependent defense pathway has been associated with resistance to Colletotrichum spp. and the other pathogens. To better understand the SA-mediated defense mechanisms in strawberry, we analyzed two strawberry cultivars treated with SA for their resistance to anthracnose and gene expression profiles at 6, 12, 24, and 48 hr post-treatment. Strawberry genes related to SA biosynthesis, perception, and signaling were identified from SA-responsive transcriptomes of the two cultivars, and the induction of 17 candidate genes upon SA treatment was confirmed by qRT-PCR. Given the pivotal role of the non-expressor of pathogenesis-related (NPR) family in controlling the SA-mediated defense signaling pathway, we then analyzed NPR orthologous genes in strawberry. From the expression profile, FaNPRL-1 [ortholog of FvNPRL-1 (gene20070 in F. vesca)] was identified as an NPR-like gene significantly induced after SA treatment in both cultivars. With a conserved BTB/POZ domain, ankyrin repeat domain, and nuclear localization signal, FvNPRL-1 was found phylogenetically closer to NPR3/NPR4 than NPR1 in Arabidopsis. Ectopic expression of FvNPRL-1 in the Arabidopsis thaliana wild type suppressed the SA-mediated PR1 expression and the resistance to Pseudomonas syringae pv. tomato DC3000. Transient expression of FvNPRL-1 fused with green fluorescent protein in Arabidopsis protoplasts showed that SA affected nuclear translocation of FvNPRL-1. FvNPRL-1 likely functions similar to Arabidopsis NPR3/NPR4 as a negative regulator of the SA-mediated defense.


Molecular characterization of five porcine candidate genes for drip loss in pork.
Drip loss is the loss of fluid from a piece of meat without mechanical force and represents an important meat quality trait. Previous work revealed a quantitative trait locus (QTL) for drip loss in pork in an experimental Duroc x Pietrain (DUPI) F2 family on SSC 5. Based on functional data indicating their possible involvement in water holding capacity and their expression in skeletal muscle, we selected five positional candidates (ACO2, ADSL, CBY1, KCNJ4, PLA2AG6) out of 130 predicted genes in the QTL interval for further analysis. We performed a mutation analysis of all coding exons and discovered 204 polymorphisms. We genotyped 39 single nucleotide polymorphisms (SNPs) in 192 Pietrain pigs with extreme drip loss phenotypes and detected a possible association with drip loss for one non-coding SNP in the ADSL gene (ss107793818, p(raw) = 0.021). Correspondingly, ADSL diplotypes were associated with drip loss and pH1 of M. longissimus dorsi. However, after correction for multiple testing, none of the tested SNPs were significantly associated with drip loss. One possible explanation for these results is that one of the QTL-alleles from the experimental DUPI family may be fixed or nearly fixed in the tested Pietrain population.


Spectrally Tunable Sources for Advanced Radiometric Applications.
A common radiometric platform for the development of application-specific metrics to quantify the performance of sensors and systems is described. Using this platform, sensor and system performance may be quantified in terms of the accuracy of measurements of standardized sets of source distributions. The prototype platform consists of spectrally programmable light sources that can generate complex spectral distributions in the ultraviolet, visible and short-wave infrared regions for radiometric, photometric and colorimetric applications. In essence, the programmable spectral source is a radiometric platform for advanced instrument characterization and calibration that can also serve as a basis for algorithm testing and instrument comparison.


Usefulness of Venous Pressure Measurement in Endovascular Treatment of Budd-Chiari Syndrome: A Retrospective Cohort Study.
Objective Therapeutic predictors derived from the venous pressure before therapy have not been identified for Budd-Chiari syndrome (BCS). The aim of this study was to determine whether or not measuring the distal pressure or pressure gradient was useful for predicting treatment efficacy in BCS. Methods We retrospectively analyzed seven consecutive patients diagnosed with symptomatic BCS at our hospital between 2008 and 2017. Distal and proximal venous pressures at occlusion sites of BCS were measured before treatment in all cases. The pressure gradient was defined as the difference between distal and proximal venous pressures. A receiver operating characteristics (ROC) analysis was performed for venous pressures. Results Percutaneous old balloon angioplasty (POBA) was performed in seven cases, with technical success achieved in all cases (100%). No complications were encountered. The median primary patency was 574 (interquartile range, 439.5-1,056.5) days. The 1-year primary patency rate was 71.73%. Six cases (85.7%) showed resolution of symptoms, representing clinical success. The ROC analysis revealed a high distal pressure (area under the ROC curve = 0.83, cut-off=12 mmHg) as a predictor of treatment efficacy of POBA for symptomatic BCS. In addition, the pressure gradient was considered significant from a clinical perspective, because the 6 successful cases with resolution of symptoms showed a large pressure gradient (range, 8-21 mmHg) before treatment, whereas the failed case showed a relatively small pressure gradient (7 mmHg). Conclusion High distal pressure and a large pressure gradient might predict the treatment efficacy of balloon angioplasty for symptomatic BCS.


Comparison of alignment and spondylolysis fracture angle in bilateral and unilateral spondylolysis.
Spondylolysis occurs bilaterally or unilaterally and bilateral spondylolysis increases the risk of developing isthmic spondylolisthesis. The characteristics of the lumbar lordosis angle (LLA), sacral slope angle (SSA), and spondylolysis fracture angle (SFA) in bilateral spondylolysis compared with those in unilateral spondylolysis have not been clarified. The purpose of this study was to compare the LLA, SSA, and SFA of bilateral and unilateral spondylolysis. Thirty-eight patients with lumbar spondylolysis who visited our clinic for an initial visit and 15 age-matched patients with a chief complaint of low back pain were included as controls. Computed tomography films were used to classify all spondylolysis patients into two groups: those with bilateral fractures (bilateral) and those with unilateral fractures (unilateral). The LLA and SSA were measured using lateral X-ray films and the SFA was measured using computed tomography films. The LLA was significantly higher in all spondylolysis patients than in the control group (p = .026). There was no significant difference in SSA between the spondylolysis and control groups (p = .28). The LLA was significantly higher in the bilateral group than in the unilateral group (p = .018). There was no significant difference in SSA between the bilateral and unilateral groups (p = .15). The SFA was significantly lower in the bilateral group than in the unilateral group (p = .024). This study suggests that physical therapy for spondylolysis may be considered bilaterally and unilaterally.


T cell proliferation in Mycobacterium lepraemurium infection. II. Characterization of cells that transfer resistance in subcutaneously infected mice.
T lymphocyte proliferation, Lyt phenotypes and their role in the evolution of protective immunity were studied in BALB/c and C57BL/6 mice infected subcutaneously with Mycobacterium lepraemurium. Antigen-induced proliferation was not demonstrable with T-enriched cells obtained from the spleens. However, these cells were capable of spontaneously proliferating in the absence of added antigen for a limited period. This proliferation was dependent on the presence of a phagocytic and adherent accessory cell. During the period when the T cells proliferated spontaneously they consisted of a mixture of Lyt-1 and Lyt-23 and were able to transfer protection to syngeneic recipient mice. Furthermore, the multiplication of the organisms was curbed during the same period demonstrating a strong association between the ability to proliferate spontaneously Lyt-1/Lyt-23 cells and protective immunity. T cells from normal BALB/c mice showed a marked suppressive effect on protection suggesting that these cells may be responsible for the susceptibility of this strain to a moderate subcutaneous infection.


Thumb polydactyly: clinical outcome after reconstruction.
To evaluate clinical and cosmetic outcomes of reconstruction in thumb polydactyly and prognostic value of the Wassel classification. Between 1993 and 2000 inclusive, out of the patients with thumb polydactyly (involving 80 thumbs) operated on, 34 patients (36 thumbs) were available for review and underwent clinical and radiological assessment. Outcomes in terms of the Tada score and complications were recorded. The mean age of patients at the time of operation was 2.8 (range, 0.6-47) years. The mean follow-up period was 5 (range, 2.4-10) years. According to the Wassel classification, 12 were type-II thumb polydactyly, 3 type-III, 11 type-IV, 6 type-V, one type-VI, and 3 type-VII. There was no perioperative mortality or wound infection. More than 88% of the patients were satisfied or very satisfied with functional and cosmetic outcomes. Postoperative complications such as scar hypertrophy, pulp atrophy, joint deformity, and instability were common but minor. Ridge nail deformity after the Bilhaut Cloquet procedure was amenable to secondary corrective procedures. All types of operated thumb polydactyly achieved similar mean Tada scores (14.7- 16.6 out of 20). The Wassel classification category, age, and surgical procedures were found to have no prognostic value with regard to the Tada score and presence of complications. Surgery on thumb polydactyly is rewarding. The Wassel classification category can be used as a guide for treatment, although it fails to predict the occurrence of postoperative complications or Tada scores. Our patients' results can serve as guidelines of expected outcomes after reconstructive procedures in different sub-types of thumb polydactyly.


Learning to Live With HIV in the Rural Townships: A Photovoice Study of Men Who Have Sex With Men Living With HIV in Mpumalanga, South Africa.
There is limited understanding about the health and well-being of men who have sex with men (MSM) with HIV infection living in rural African areas. We present the results of an adapted photovoice project with 35 MSM with HIV infection who live in townships in Mpumalanga, South Africa. The project was designed to explore the social factors that influenced HIV care. Twenty-four photo essays were developed by participants in focus group discussions that were audio-recorded and transcribed for analysis. Transcripts and photo essays were coded using a constant comparison approach combining researcher observation notes and reflection on participant-identified themes. Participants identified (a) a shared experience of illness and coming to terms with having HIV infection and (b) family and taverns as necessary support systems. The findings suggested that family- and tavern-based interventions might improve health outcomes for MSM newly diagnosed with HIV infection living in rural and semi-rural African communities.


Comparative studies on the efficacy of brotizolam and nitrazepam: a multi-centre study.
Efficacy and tolerability of brotizolam (0.25 and 0.5 mg) were compared over a 6-day period with nitrazepam (5.0 mg) in middle-aged patients (less than 65 years) with sleep disturbances requiring medication. The study was double-blind and randomised with a cross-over design. Each preparation reduced sleep onset latency and frequency of awakenings, and improved quality and duration of sleep as well as subjective condition on awakening. Brotizolam 0.25 mg was found to be equally effective as 0.5 mg, and so the lower dose is recommended for the middle aged.


Development and characterization of films based on chemically cross-linked gliadins.
The aim of the present work has been to study the possibility of obtaining modified gliadin films with improved water resistance and mechanical properties by means of promoting intermolecular covalent bonds between polypeptide chains. Prior to casting films, formaldehyde, glutaraldehyde, and glyoxal were used to cross-link proteins at concentrations ranging from 1% to 4% (grams per 100 g of protein). Mechanical properties (tensile strength and elongation at break), water vapor permeability, moisture sorption isotherms, and optical properties of the films produced were evaluated as a function of the cross-linker used. Experimental results showed that some properties of gliadin films were considerably modified. Cross-linking improved the water resistance of films, avoiding their disintegration. Their water barrier properties were also enhanced, but their moisture sorption properties remained unchanged. Formaldehyde imparted greater mechanical strength to films than glutaraldehyde or glyoxal, increasing tensile strength values 10-fold. Addition of the cross-linkers at concentrations in excess of 2.5% did not further improve the mechanical or barrier properties. However, modification with glutaraldehyde or glyoxal imparted an increasingly yellowish tint to the films.


MASPs at the crossroad between the complement and the coagulation cascades - the case for COVID-19.
Components of the complement system and atypical parameters of coagulation were reported in COVID-19 patients, as well as the exacerbation of the inflammation and coagulation activity. Mannose binding lectin (MBL)- associated serine proteases (MASPs) play an important role in viral recognition and subsequent activation of the lectin pathway of the complement system and blood coagulation, connecting both processes. Genetic variants of MASP1 and MASP2 genes are further associated with different levels and functional efficiency of their encoded proteins, modulating susceptibility and severity to diseases. Our review highlights the possible role of MASPs in SARS-COV-2 binding and activation of the lectin pathway and blood coagulation cascades, as well as their associations with comorbidities of COVID-19. MASP-1 and/or MASP-2 present an increased expression in patients with COVID-19 risk factors: diabetes, arterial hypertension and cardiovascular disease, chronic kidney disease, chronic obstructive pulmonary disease, and cerebrovascular disease. Based also on the positive results of COVID-19 patients with anti-MASP-2 antibody, we propose the use of MASPs as a possible biomarker of the progression of COVID-19 and the investigation of new treatment strategies taking into consideration the dual role of MASPs, including MASP inhibitors as promising therapeutic targets against COVID-19.


Preoperative anxiety in preschool children: A randomized clinical trial comparing midazolam, clonidine, and dexmedetomidine.
Anxiety in pediatric patients may challenge perioperative anesthesiology management and worsen postoperative outcomes. Sedative drugs aimed to reducing anxiety are available with different pharmacologic profiles, and there is no consensus on their effect or the best option for preschool children. In this study, we aimed to compare the effect of three different premedications on anxiety before anesthesia induction in preschool children aged 2-6 years scheduled for elective surgery. The secondary outcomes comprised distress during peripheral catheter (PVC) insertion, compliance at anesthesia induction, and level of sedation. In this double-blinded randomized clinical trial, we enrolled 90 participants aged 2-6 years, who were scheduled for elective ear-, nose-and-throat surgery. The participants were randomly assigned to three groups: those who were administered 0.5 mg/kg oral midazolam, 4 µg/kg oral clonidine, or 2 µg/kg intranasal dexmedetomidine. Anxiety, distress during PVC insertion, compliance with mask during preoxygenation, and sedation were measured using the modified Yale Preoperative Anxiety Scale, Behavioral Distress Scale, Induction Compliance Checklist, and Ramsay Sedation Scale, respectively. Six children who refused premedication were excluded, leaving 84 enrolled patients. At baseline, all groups had similar levels of preoperative anxiety and distress. During anesthesia preparation, anxiety was increased in the children who received clonidine and dexmedetomidine; however, it remained unaltered in the midazolam group. There were no differences in distress during PVC insertion or compliance at induction between the groups. The children in the clonidine and dexmedetomidine groups developed higher levels of sedation than those in the midazolam group. In preschool children, midazolam resulted in a more effective anxiolysis and less sedation compared to clonidine and dexmedetomidine.


Prediction of challenge test results by flour-specific IgE and skin prick test in symptomatic bakers.
Wheat and rye flours are among the most important allergens causing occupational asthma. Usually, the diagnosis of baker's asthma is based on inhalation challenge tests with flours. To evaluate the relevance of flour-specific serum immunoglobulin E (IgE) and skin prick test (SPT) in the diagnosis of baker's asthma and to define flour-specific IgE concentrations and wheal sizes that allow a prediction of the outcome of challenge testing. Bronchial and nasal challenge tests with wheat (rye) flour were performed in 71 (95) symptomatic bakers. Determinations of flour-specific IgE as well as SPTs were performed in all subjects. Analyses included the calculation of sensitivity, specificity, positive (PPV) and negative predictive values (NPV) at different IgE concentrations and different wheal sizes, and receiver-operating characteristics (ROC) plots with the challenge result as gold standard. Thirty-seven bakers were positive in the challenge with wheat flour, while 63 were positive with rye flour. Depending on the flour-specific IgE concentrations (wheal size), PPV was 74-100% (74-100%) for wheat and 82-100% (91-100%) for rye flour, respectively. The minimal cut-off values with a PPV of 100% were 2.32 kU/l (5.0 mm) for wheat flour and 9.64 kU/l (4.5 mm) for rye flour. The shapes of the ROC plots were similar for wheat and rye flour. High concentrations of flour-specific IgE and clear SPT results in symptomatic bakers are good predictors for a positive challenge test. Challenge tests with flours may be avoided in strongly sensitized bakers.


Genomic and transcriptomic survey of an endophytic fungus Calcarisporium arbuscula NRRL 3705 and potential overview of its secondary metabolites.
Secondary metabolites as natural products from endophytic fungi are important sources of pharmaceuticals. However, there is currently little understanding of endophytic fungi at the omics levels about their potential in secondary metabolites. Calcarisporium arbuscula, an endophytic fungus from the fruit bodies of Russulaceae, produces a variety of secondary metabolites with anti-cancer, anti-nematode and antibiotic activities. A comprehensive survey of the genome and transcriptome of this endophytic fungus will help to understand its capacity to biosynthesize secondary metabolites and will lay the foundation for the development of this precious resource. In this study, we reported the high-quality genome sequence of C. arbuscula NRRL 3705 based on Single Molecule Real-Time sequencing technology. The genome of this fungus is over 45 Mb in size, larger than other typical filamentous fungi, and comprises 10,001 predicted genes, encoding at least 762 secretory-proteins, 386 carbohydrate-active enzymes and 177 P450 enzymes. 398 virulence factors and 228 genes related to pathogen-host interactions were also predicted in this fungus. Moreover, 65 secondary metabolite biosynthetic gene clusters were revealed, including the gene cluster for the mycotoxin aurovertins. In addition, several gene clusters were predicted to produce mycotoxins, including aflatoxin, alternariol, destruxin, citrinin and isoflavipucine. Notably, two independent gene clusters were shown that are potentially involved in the biosynthesis of alternariol. Furthermore, RNA-Seq assays showed that only expression of the aurovertin gene cluster is much stronger than expression of the housekeeping genes under laboratory conditions, consistent with the observation that aurovertins are the predominant metabolites. Gene expression of the remaining 64 gene clusters for compound backbone biosynthesis was all lower than expression of the housekeeping genes, which partially explained poor production of other secondary metabolites in this fungus. Our omics data, along with bioinformatics analysis, indicated that C. arbuscula NRRL 3705 contains a large number of biosynthetic gene clusters and has a huge potential to produce a profound number of secondary metabolites. This work also provides the basis for development of endophytic fungi as a new resource of natural products with promising biological activities.


Blood Feeding Patterns of Aedes aegypti Populations in Senegal.
Aedes aegypti plays an important role in the transmission of several arboviruses of medical importance. The availability of information on the blood-feeding preferences of mosquito vectors is a critical step in the understanding of the transmission of human pathogens and implementation of control strategies. In Senegal, no data currently exist on the feeding pattern of Ae. aegypti in urban areas. To fill this gap, Ae. aegypti blood-fed females were collected in five localities by aspiration and using BG Sentinel 2 traps. Collections were carried out monthly between July and November 2019 inside and outside human dwellings. The origin of the blood meal of Ae. aegypti females were identified by an ELISA technique. A total of 1,710 blood-engorged females were examined and showed that Ae. aegypti preferentially fed on human with 78.6% of the identified blood meals. The other blood meals were from animals including dog, cat, horse, cattle, sheep, and rat. This is the first report on the feeding behavior of Ae. aegypti in urban settings in West Africa. It demonstrated that this species is highly anthropophilic.


Biofiltration with bicarbonate as dialysate buffer.
The biofiltration with bicarbonate as dialysate buffer (BiBF) was used in 10 patients on RDT: the patients were treated for 10 months on standard BF and for 10 months on BiBF. The amount of fluid infused varied between 3 and 5 liters and Na-bicarbonate (100 mEq/h) was infused during BF. The dialytic protocol was 3 hours every other day. Cardiovascular stability, waste molecules and acid-base balance were investigated. No differences in vascular stability and no significant changes in the waste-molecules concentrations were found. Both protocols correct the metabolic acidosis; however, in standard BF 50% of patients showed acute hypocapnia at the end of dialysis.


High frequency of intestinal TH17 cells correlates with microbiota alterations and disease activity in multiple sclerosis.
T helper 17 (TH17) cells are key players in multiple sclerosis (MS), and studies in animal models demonstrated that effector TH17 cells that trigger brain autoimmunity originate in the intestine. We validate in humans the crucial role of the intestinal environment in promoting TH17 cell expansion in MS patients. We found that increased frequency of TH17 cells correlates with high disease activity and with specific alterations of the gut mucosa-associated microbiota in MS patients. By using 16S ribosomal RNA sequencing, we analyzed the microbiota isolated from small intestinal tissues and found that MS patients with high disease activity and increased intestinal TH17 cell frequency showed a higher Firmicutes/Bacteroidetes ratio, increased relative abundance of Streptococcus, and decreased Prevotella strains compared to healthy controls and MS patients with no disease activity. We demonstrated that the intestinal TH17 cell frequency is inversely related to the relative abundance of Prevotella strains in the human small intestine. Our data demonstrate that brain autoimmunity is associated with specific microbiota modifications and excessive TH17 cell expansion in the human intestine.


Routine Use of Contact Precautions for Methicillin-Resistant Staphylococcus aureus and Vancomycin-Resistant Enterococcus: Which Way Is the Pendulum Swinging?
BACKGROUND Studies have suggested that contact precautions (CP) for methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococcus may have risks that outweigh the benefits. These risks, coupled with more widespread use of horizontal interventions such as daily bathing with chlorhexidine gluconate, have brought into question the value of routine CP for these organisms. OBJECTIVE To assess the state of utilization of CP as well as adjunctive measures to reduce the risk of transmission in US hospitals. DESIGN Cross-sectional survey. PARTICIPANTS Total of 751 physician members of the Emerging Infections Network. METHODS An 8-question electronic survey distributed by email. RESULTS A total of 426/751 (57%) responded to the survey; 337/364 (93%) of respondents use routine CP for methicillin-resistant S. aureus and 335/364 (92%) use routine CP for vancomycin-resistant enterococcus. The most widely used trigger for initiation of CP for both pathogens was positive clinical culture. Practices for discontinuation of isolation varied widely. We found that 325/354 (92%) perform routine chlorhexidine gluconate bathing and 236/353 (67%) perform S. aureus decolonization with mupirocin for 1 or more subsets of inpatients, and 82/356 (23%) reported using either hydrogen peroxide vapor or ultraviolet-C room disinfection at discharge. Free text responses noted frustration and variation in the application, practice, and process for initiation and discontinuation of CP. CONCLUSIONS Use of CP for methicillin-resistant S. aureus and vancomycin-resistant enterococcus remains commonplace, although horizontal interventions such as chlorhexidine gluconate bathing are increasingly used. The heterogeneity of practices and policies was striking. Evidence-based guidelines regarding CP and horizontal interventions are needed. Infect. Control Hosp. Epidemiol. 2015;37(1):36-40.


Immunoprophylaxis for influenza: comparison of a subunit and a whole virion vaccine.
In order to evaluate and compare immunogenicity, reactogenicity and protection of a subunit vaccine and a whole virus vaccine 102 elderly subjects were vaccined against influenza in November 1986: 53 received the subunit vaccine and 49 were immunized with the whole virus preparation. Local and systemic reactions following immunization, as well as the presence of influenza clinical symptoms were recorded throughout the study period (November 1986 - June 1987). Antibodies against influenza were detected using the Single Radial Haemolysis (S.R.H.) technique on two serum samples obtained from volunteers prior to immunization and 1 month later. The subunit vaccine showed equal immunogenicity, equal protection and lower reactogenicity as compared with the whole virus preparation.


The differentiation of pancreatic tumor-initiating cells by vitronectin can be blocked by cilengitide.
Pancreatic cancer is a leading cancer type and its molecular pathology is poorly understood. The only potentially curative therapeutic option available is complete surgical resection; however, this is inadequate as most of the patients are diagnosed at an advanced or metastatic stage. Tumor-initiating cells (TICs) constitute a subpopulation of cells within a solid tumor that sustain tumor growth, metastasis, and chemo/radioresistance. Within pancreatic cancer, TICs have been identified based on the expression of specific cell surface markers. We use a sphere formation assay to enrich putative TICs and use human serum as a driver of differentiation. We demonstrate by using specific blocking reagents that we can inhibit the differentiation process and maintain TIC-associated markers and genes. We can induce differentiation of pancreatospheres with the addition of human serum, and we identified vitronectin as an inducer of differentiation. We inhibit differentiation by human serum using an arginine-glycine-aspartate-specific peptide, which is Cilengitide; hence, demonstrating this differentiation is mediated via specific integrin receptors. Overall, our studies further the definition of pancreatic TICs and provide further insight into both the maintenance and differentiation of this lethal population.


Blood lymphocyte proliferation response to pollen extract as a monitor of immunotherapy.
In a study of immunotherapy 41 children with seasonal rhinoconjunctivitis due to deciduous tree pollen allergy were monitored by means of symptom scoring, patient self-evaluation, conjunctival provocation tests and lymphocyte proliferation in vitro to the allergen. The lymphocyte responsiveness to birch pollen decreased significantly during the first year of immunotherapy. However, neither the lymphocyte responsiveness before treatment nor changes in lymphocyte reactivity during the immunotherapy correlated with the clinical efficacy of the therapy as evaluated by changes in symptom scores, self-evaluation or conjunctival provocation test changes in the individual patients. The results indicate that lymphocyte responsiveness to an allergen cannot be used to select patients for immunotherapy, i.e. to predict whether a patient would benefit from immunotherapy or not, or to evaluate the effects of immunotherapy after beginning the treatment. However, lymphocyte proliferation response to an allergen indicates clinical sensitivity.


A Novel Truncated Form of Serum Amyloid A in Kawasaki Disease.
Kawasaki disease (KD) is an acute vasculitis in children that can cause coronary artery abnormalities. Its diagnosis is challenging, and many cytokines, chemokines, acute phase reactants, and growth factors have failed evaluation as specific biomarkers to distinguish KD from other febrile illnesses. We performed protein profiling, comparing plasma from children with KD with febrile control (FC) subjects to determine if there were specific proteins or peptides that could distinguish the two clinical states. Plasma from three independent cohorts from the blood of 68 KD and 61 FC subjects was fractionated by anion exchange chromatography, followed by surface-enhanced laser desorption ionization (SELDI) mass spectrometry of the fractions. The mass spectra of KD and FC plasma samples were analyzed for peaks that were statistically significantly different. A mass spectrometry peak with a mass of 7,860 Da had high intensity in acute KD subjects compared to subacute KD (p = 0.0003) and FC (p = 7.9 x 10-10) subjects. We identified this peak as a novel truncated form of serum amyloid A with N-terminal at Lys-34 of the circulating form and validated its identity using a hybrid mass spectrum immunoassay technique. The truncated form of serum amyloid A was present in plasma of KD subjects when blood was collected in tubes containing protease inhibitors. This peak disappeared when the patients were examined after their symptoms resolved. Intensities of this peptide did not correlate with KD-associated laboratory values or with other mass spectrum peaks from the plasma of these KD subjects. Using SELDI mass spectrometry, we have discovered a novel truncated form of serum amyloid A that is elevated in the plasma of KD when compared with FC subjects. Future studies will evaluate its relevance as a diagnostic biomarker and its potential role in the pathophysiology of KD.


Reconstitution of mitochondrial protein transport with purified ornithine carbamoyltransferase precursor expressed in Escherichia coli.
Ornithine carbamoyltransferase (OTC; subunit, 36,000 Da) is initially synthesized as a precursor (pOTC) with a transient NH2-terminal presequence of 32 amino acid residues and imported posttranslationally into the mitochondrial matrix. The rat pOTC was synthesized in Escherichia coli using an expression vector containing a thermoinducible lambda pL promoter. The recombinant pOTC represented 5-10% of the total bacterial protein and was present in the precipitate of the disrupted bacteria. The precipitate was washed and pOTC was extracted with 8 M urea or 0.1% cetyltrimethylammonium bromide. The extracted pOTC was essentially homogeneous, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The purified pOTC was cleaved to the intermediate-sized product of 37,000 Da by a processing protease partially purified from the matrix fraction of rat liver mitochondria. The purified recombinant pOTC, but not the mature form of OTC synthesized in E. coli and purified, competed with the in vitro-synthesized, radiolabeled pOTC for uptake and processing by the isolated rat liver mitochondria. The radiolabeled and purified recombinant pOTC could be imported into the isolated mitochondria and processed to the mature form in an energy- and rabbit reticulocyte lysate-dependent manner. When the purified pOTC was subjected to sucrose gradient centrifugation, it sedimented as a large aggregate of greater than 60 S in the absence of reticulocyte lysate, whereas it sedimented as a complex of about 5 S in the presence of the lysate. These observations together with our previous results indicate that a protein factor(s) present in the lysate interacts with pOTC and holds it in an import-competent form.


Gender and stress in predicting depressive symptoms following stroke.
Post-stroke depression (PSD) is associated with poor clinical and functional outcomes, and women are likely to experience PSD more than men. Although stress is related to depression, and women report greater emotional reactivity to stressful life events, the link between stress and gender is yet to be examined relative to PSD. Further, electronic momentary assessment (EMA), a mobile technology, has not been used to assess stressful life events and PSD in real time and in the natural environments of daily life. The purpose of the current study was to examine gender differences in the relationship of stress and PSD using EMA. Individuals admitted to the Stroke Center at the University of Bordeaux were contacted for participation in a prospective study of symptoms and experiences in daily life using ambulatory monitoring. Forty-three post-stroke patients (47% female) completed electronic assessments of life events, perceived stress, and depressive symptoms (i.e., sad mood, anhedonia, fatigue, concentration difficulties, appetite change, negative thoughts, hopelessness) during their daily life for one week. Patients also completed a clinician-administered standardized depression scale at baseline and three-month follow-up. Using EMA, participants responded to 83.7% of the electronic interviews for a total of 1,140 observations across diverse daily life contexts. Stressful events of any degree of negativity were reported at over one-third (37.3%) of all EMA assessments. The severity of depressive symptoms as assessed in daily life through EMA was greater in women following stroke than in men. Further, there was a significant association between EMA-assessed depressive symptoms and daily life stress for women, but not men. This association was due primarily to three specific depressive symptoms: sad mood, fatigue, and appetite change. No difference was observed between men and women in standardized depression assessments administered during clinic visits at baseline or three-month follow-up. Greater reactivity to stressful life events and a link between stress reactivity and depressive symptoms were found in female as compared to male post-stroke patients. Gender differences in depressive symptoms were identified using EMA data collected during daily life as contrasted with the use of a standard assessment during clinic visits. Mobile technologies may help to identify important real-time behaviors and symptoms that are not observable by standard clinical assessments employed at regular clinic visits. Further, future research should examine the overall and gender-specific benefits of stress-based interventions to reduce the risk of PSD for adults.


Self-regulatory coping among community dwelling older adults with multiple chronic conditions.
Many older adults with multiple chronic conditions (MCC) frequently experience hospitalizations, functional limitations, and poor quality of life. Outcomes may be improved by promoting self-regulation, which may individuals respond to health threats and manage their health conditions. The aim of this study was to describe self-regulatory coping among older adults with MCC. A qualitative descriptive study using semi-structured interviews and content analysis and guided by the Common-Sense Self-Regulation Model. Seventeen community-dwelling older adults with two or more chronic conditions participated in our study. Three themes were developed from the analysis: (1) "I don't think about it unless something happens": coping in the absence of a health event, (2) "doing what I am supposed to do": coping during a health event, and (3) "How do I know if what I did works?": appraisal of coping success. Self-regulatory coping was influenced by individual beliefs and experiences (illness representations), context, self-efficacy and availability of support and resources to cope with MCC. These findings suggest implications for clinical practice and future self-regulation interventions for older adults with MCC.


Investigational drugs in development for focal segmental glomerulosclerosis.
Focal segmental glomerulosclerosis is an important cause of end stage kidney disease and is a paradigm for the study of glomerular scarring. There are no FDA approved treatments for this condition. Current therapies, assessed based on reduction in proteinuria, are generally effective in a subset of patients which suggests that FSGS is a heterogeneous group of glomerular disorders or podocytopathies that converge on a common histopathological phenotype. Areas covered: We searched for investigational drugs agents that target different pathophysiological pathways using the key words 'FSGS' and 'podocyte' in American and European clinical trial registers (clinicaltrials.gov; clinicaltrialsregister.eu). Published articles were searched in PubMed, Medline, the Web of Science and the Cochrane Central Register of Controlled Trials Library. Expert opinion: Progress is being made in defining the mechanism of action of subtypes of FSGS. Current and investigational therapies for FSGS target these different pathways of injury. It is anticipated that advances in systems biology will further refine the classification of FSGS by subdividing the disease based on the primary mechanism of glomerular injury, identify biomarkers to discriminate between different subtypes, and enable appropriate selection of appropriate therapy for each individual in accordance with the goals of precision medicine.


Surfactin variants for intra-intestinal delivery of insulin.
Surfactin is a Bacillus-produced natural lipopeptide, which can overcome the epithelial cell barriers for orally delivering insulin, but its ability to promote uptake of insulin by the intestine need to be further improved for a higher oral bioavailability. Here, we designed and synthesized several surfactin variants to improve its ability for oral delivery of insulin. Firstly, we replaced Glu with Gln in surfactin for decreasing its negative charges, but found this replacement weakened its ability to orally delivery insulin. We further chemically synthesized surfactin variant by replacing its fatty acid chain (C15) with a shortened one (C14), and found this replacement did not influence its ability to orally deliver insulin. Lastly, we replaced its amino acids (Leu) with more hydrophobic ones (Ile), and found the replacement could significantly improve its ability to deliver insulin, with a maximal blood glucose decrease to 27.33% of the initial level and an insulin bioavailability of 18.25%. We also replaced its amino acids of Leu with Val, and Val with Ile, and found this replacement could also significantly improve its ability to deliver insulin with a maximal blood glucose decrease to 18.36% of the initial level and a high insulin bioavailability of 26.32% in diabetic mice. Further analysis by CD, we found the surfactin variants with more hydrophobic amino acid residuals significantly induced insulin from rigid (α-helix) to flexible structure (β-sheet and random coil), that is favorable for insulin to permeate across the intestine epithelial membrane. Collectively, surfactin variants with more hydrophobicity are very potential for delivery of insulin in the everyday control of blood glucose.


Effect of Nitrite and Nitrate Concentrations on the Performance of AFB-MFC Enriched with High-Strength Synthetic Wastewater.
In order to study the effect of nitrite and nitrate on the performance of microbial fuel cell, a system combining an anaerobic fluidized bed (AFB) and a microbial fuel cell (MFC) was employed for high-strength nitrogen-containing synthetic wastewater treatment. Before this study, the AFB-MFC had been used to treat high-strength organic wastewater for about one year in a continuous flow mode. The results showed that when the concentrations of nitrite nitrogen and nitrate nitrogen were increased from 1700 mg/L to 4045 mg/L and 545 mg/L to 1427 mg/L, respectively, the nitrite nitrogen and nitrate nitrogen removal efficiencies were both above 99%; the COD removal efficiency went up from 60.00% to 88.95%; the voltage was about 375 ± 15 mV while the power density was at 70 ± 5 mW/m(2). However, when the concentrations of nitrite nitrogen and nitrate nitrogen were above 4045 mg/L and 1427 mg/L, respectively, the removal of nitrite nitrogen, nitrate nitrogen, COD, voltage, and power density were decreased to be 86%, 88%, 77%, 180 mV, and 17 mW/m(2) when nitrite nitrogen and nitrate nitrogen were increased to 4265 mg/L and 1661 mg/L. In addition, the composition of biogas generated in the anode chamber was analyzed by a gas chromatograph. Nitrogen gas, methane, and carbon dioxide were obtained. The results indicated that denitrification happened in anode chamber.


Functional involvement of endothelial lipase in hepatitis B virus infection.
HBV infection causes chronic liver disease and leads to the development of HCC. To identify host factors that support the HBV life cycle, we previously established the HC1 cell line that maintains HBV infection and identified host genes required for HBV persistence. The present study focused on endothelial lipase (LIPG), which binds to heparan sulfate proteoglycans (HSPGs) in the cell membrane. We found HBV infection was impaired in humanized liver chimeric mouse-derived hepatocytes that were transduced with lentivirus expressing short hairpin RNA against LIPG. Long-term suppression of LIPG combined with entecavir further suppressed HBV replication. LIPG was shown to be involved in HBV attachment to the cell surface by using 2 sodium taurocholate cotransporting peptide (NTCP)-expressing cell lines, and the direct interaction of LIPG and HBV large surface protein was revealed. Heparin and heparinase almost completely suppressed the LIPG-induced increase of HBV attachment, indicating that LIPG accelerated HBV attachment to HSPGs followed by HBV entry through NTCP. Surprisingly, the attachment of a fluorescently labeled NTCP-binding preS1 probe to NTCP-expressing cells was not impaired by heparin, suggesting the HSPG-independent attachment of the preS1 probe to NTCP. Interestingly, attachment of the preS1 probe was severely impaired in LIPG knockdown or knockout cells. Inhibitors of the lipase activity of LIPG similarly impaired the attachment of the preS1 probe to NTCP-expressing cells. LIPG participates in HBV infection by upregulating HBV attachment to the cell membrane by means of 2 possible mechanisms: increasing HBV attachment to HSPGs or facilitating HSPG-dependent or HSPG-independent HBV attachment to NTCP by its lipase activity.


Spontaneous tibial artery thrombosis associated with varicella pneumonia and free protein S deficiency.
Pneumonia is the most common serious complication of varicella infection in adults. A variety of thrombotic complications including purpura fulminans and disseminated intravascular coagulation have been reported in children with varicella but not in adults. Two men with varicella pneumonia who had profound lower extremity ischemia caused by thrombosis of the profunda femoris and tibial arteries are reported. Both patients had free protein S deficiency and vascular thrombosis in association with varicella pneumonia without overt evidence of disseminated intravascular coagulation or purpura fulminans. Antiphospholipid immunoglobulin G and immunoglobulin M antibodies were present in one, whereas the other had evidence of the lupus anticoagulant. The proposed pathogenesis and management options including intraarterial thrombolytic therapy with urokinase and the need for long-term anticoagulation are discussed.


Activity-dependent gene expression correlates with interictal spiking in human neocortical epilepsy.
Interictal spikes are hallmarks of epileptic neocortex that are used commonly in both EEG and electrocorticography (ECoG) to localize epileptic brain regions. Despite their prevalence, the exact relationship between interictal spiking and the molecular pathways that drive the production and propagation of seizures is not known. We have recently identified a common group of genes induced in human epileptic foci, including EGR1, EGR2, c-fos, and MKP-3. We found that the expression levels of these genes correlate precisely with the frequency of interictal activity and can thus serve as markers of epileptic activity. Here, we explore this further by comparing the expression of these genes within human epileptic neocortex to both ictal and specific electrical parameters of interictal spiking from subdural recordings prior to surgical resection in order to determine the electrical properties of the human neocortex that correlate best to the expression of these genes. Seizure frequency as well as quantitative electrophysiological parameters of interictal spikes including frequency, amplitude, duration, and area were calculated at each electrode channel and compared to quantitative real-time RT-PCR measurements of four activity-dependent genes (c-fos, EGR1, EGR2, and MKP-3) in the underlying neocortical tissue. Local neocortical regions of seizure onset had consistently higher spike firing frequencies and higher spike amplitudes compared to nearby "control" cortex. In contrast, spike duration was not significantly different between these two areas. There was no relationship observed between seizure frequency and the expression levels of activity-dependent genes for the patients examined in this study. However, within each patient, there were highly significant correlations between the expression of three of these genes (c-fos, EGR1, EGR2) and the frequency, amplitude, and total area of the interictal spikes at individual electrodes. We conclude that interictal spiking is closely associated with the expression of a group of activity-dependent transcription factors in neocortical human epilepsy. Since there was little correlation between gene expression and seizure frequency, our results suggest that interictal spiking is a stronger driving force behind these activity-dependent gene changes and may thus participate in the development and maintenance of the abnormal neuronal hyperactivity seen in human epileptic neocortex.


Phytochemical investigation and antifeedant activity of Premna latifolia leaves.
The essential oil of Premna latifolia Roxb. was obtained by hydrodistillation of fresh leaves of the plant having an oil yield of 0.05%, both non-polar and essential oil were analysed by GC and GC-MS. Hexane fraction of the leaves of P. latifolia was transesterified and analysed by GC and GC-MS, 40 non-polar components were identified comprising 89.3%. The most abundant fatty acid constituents were hexadecanoic acid (25.04%), 8,11,14-docosatrienoic acid (13.62%), octadecanoic acid (6.82%), 9,12-octadecadienoic acid (4.19%) and 29 components were investigated in the essential oil which comprises 78.1%. The most abundant oil constituents were 1-octen-3-ol (35.69%), terpendiol II (7.19%), δ-guaiene (7.49%) 2-undecanone (4.80%) and α-pinene (3.27%). Different extracts were also tested against polyphagous crop pest Spodoptera litura for antifeedant activity. Essential oil showed maximum growth reduction of 56.83% followed by chloroform extract of 43.93%.


Electric field-induced selective catalysis of single-molecule reaction.
Oriented external electric fields (OEEFs) offer a unique chance to tune catalytic selectivity by orienting the alignment of the electric field along the axis of the activated bond for a specific chemical reaction; however, they remain a key experimental challenge. Here, we experimentally and theoretically investigated the OEEF-induced selective catalysis in a two-step cascade reaction of the Diels-Alder addition followed by an aromatization process. Characterized by the mechanically controllable break junction (MCBJ) technique in the nanogap and confirmed by nuclear magnetic resonance (NMR) in bottles, OEEFs are found to selectively catalyze the aromatization reaction by one order of magnitude owing to the alignment of the electric field on the reaction axis. Meanwhile, the Diels-Alder reaction remained unchanged since its reaction axis is orthogonal to the electric fields. This orientation-selective catalytic effect of OEEFs reveals that chemical reactions can be selectively manipulated through the elegant alignment between the electric fields and the reaction axis.


The effect of aluminium upon the activity of selected bone marrow enzymes in rats.
This study was carried out on male Wistar rats. The bone marrow activities of acetylcholinesterase (AchE-EC.188.8.131.52.), glutathione reductase (GR-EC.220.127.116.11.) and glucose-6-phosphate dehydrogenase (G6PD-EC.18.104.22.168.) were determined as affected by aluminium. The present experiments have revealed that within the first days there will be an increase in enzyme activity in the bone marrow. Simultaneously a decline in the activity of bone marrow could be observed which occurred later in the first course of the experiment.


Analysis of the myoglobin gene in heart disease.
Analysis of the myoglobin gene from a large number of patients with cardiac disease disclosed a single substantive mutation. However, no evidence of biochemical or physiological dysfunction due to this mutation was detected. We conclude that, within the limits of presently available techniques, myoglobin mutations are unlikely to contribute substantially to the genotypic background of cardiac disease in the general population.


Social networking sites and educational adaptation in higher education: a case study of Chinese international students in New Zealand.
This study aims to find out the relationship between the use of SNSs and educational adaptation process of Chinese international students (from China) in New Zealand. Based on interview data, this paper addressed how Chinese international students use SNSs (RenRen, Facebook, etc.) to expand and manage their online social networks to help their adaptation to new educational environment. As a case study of Chinese international students in New Zealand and from the narrative of students, we examined the relationship among educational difficulties, life satisfaction, and the use of SNSs. This study would help in further understanding how and why SNSs can be adopted in higher education to support effective overseas learning experiences.


Microneurography and sympathetic nerve activity: a decade-by-decade journey across 50 years.
The technique of microneurography has advanced the field of neuroscience for the past 50 years. While there have been a number of reviews on microneurography, this paper takes an objective approach to exploring the impact of microneurography studies. Briefly, Web of Science (Thomson Reuters) was used to identify the highest citation articles over the past 50 years, and key findings are presented in a decade-by-decade highlight. This includes the establishment of microneurography in the 1960s, the acceleration of the technique by Gunnar Wallin in the 1970s, the international collaborations of the 1980s and 1990s, and finally the highest impact studies from 2000 to present. This journey through 50 years of microneurographic research related to peripheral sympathetic nerve activity includes a historical context for several of the laboratory interventions commonly used today (e.g., cold pressor test, mental stress, lower body negative pressure, isometric handgrip, etc.) and how these interventions and experimental approaches have advanced our knowledge of cardiovascular, cardiometabolic, and other human diseases and conditions.


Tethered cord in a patient with multiple vertebral segmentation defects: a case report.
Short trunk dwarfism with multiple vertebral segmentation defects (MVSD) represents a heterogeneous group of disorders characterized by the presence of multiple vertebral and rib abnormalities. A two and one-half year-old female with the spondylothoracic dysostosisform of MVSD is presented. In addition to skeletal anomalies, a lumbar hemangioma, bilateral foot deformities, distal leg atrophy and weakness, and areflexia at the ankles were present. An underlying neuropathic process was suspected. Results of urodynamic studies were suggestive of a neurogenic bladder. Magnetic resonance imaging of the spine demonstrated a tethered spinal cord. Although various brain and spinal cord anomalies have been described in MVSD, this is the first reported case, to our knowledge, of a tethered spinal cord in a patient with MVSD. We recommend that the management of patients with MVSD include comprehensive neurological evaluation and monitoring with appropriate electrodiagnostic, urodynamic, and neuroimaging studies.


Preliminary characterization of an inhibitory activity of fetal bovine serum on the infectivity of rotavirus strain SA-11.
In the present work we studied non antibody inhibiting activity present in fetal bovine serum and active to Rotavirus infectivity and growth in cell cultures. This inhibitor was revealed by an in vitro neutralization test and characterized by gel filtration and chemical and enzymatic treatments. Furthermore, commercial preparations of bovine serum proteins were tested for inhibitory activity. Our results show that serum inhibition is partially resistant to trypsin and neuraminidase treatments but completely destroyed by KIO4. A similar activity was observed in a commercial serum bovine fraction containing predominantly alpha-globulins. These results seem to indicate that glycoproteins, and their glucidic components are the molecules predominantly involved in serum inhibition towards Rotavirus infectivity.


Interaction of interferons with skin reactive cytokines: from interleukin-1 to interleukin-8.
The skin as an organ contains a large pool of cells, important for the production of various cytokines. This study focuses on interferon-beta (IFN-beta), interleukin-6 (IL-6), and interleukin-8 (IL-8) production by fibroblasts and epithelial cells in response to interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha). Both these primary cytokines show multiple biologic activities in the skin. Their antiviral activity on fibroblasts is mediated by IFN-beta and not by IL-6. In addition, TNF-alpha and IL-1 have a growth stimulatory effect on dermal fibroblasts, which is not mediated by IFN-beta or IL-6. IL-1, double-stranded RNA, or virus are potent inducers of IL-6 and IL-8 on dermal fibroblasts, but they are less efficient on epidermal cells. IL-8 has been discovered as an early acting skin reactive factor responsible for the chemotaxis of neutrophilic granulocytes. Furthermore, IL-1 possesses delayed skin reactivity upon intradermal injection which presumably is mediated by local release of IL-8. These findings demonstrate that cytokines also interact in the skin and that dermal fibroblasts play an important role in the regulation of aspecific host defense.


Computer processing of phrenic neurograms.
Manual processing of large numbers of electrophysiological waveforms is a tedious process prone to subjective errors in judgment. To eliminate these problems, we developed computer algorithms and techniques to analyze cat phrenic neurograms produced in response to step changes in end-tidal PCO2. The computer analyzed the neurogram in terms of a model waveform, which consisted of 1) base-line activity made up primarily of noise, 2) an initial sharp increase from base line, 3) a slower ramplike increase in activity, 4) a peak value, and 5) a rapid decrease in activity back to base line. Parameters describing these model elements as well as inspiratory and expiratory times were calculated by the computer. Computer-produced parameters were compared with manually calculated parameters from chart recordings for over 200 individual neurograms. Repeated manual processing of the neurogram had a variability of +/- 10% in the parameter estimates. The computer-produced parameters fell within this range more than 89% of the time. Although the techniques described are directed specifically toward phrenic neurogram analysis, the methods are general enough to be useful in computer processing of other types of physiological waveforms.


Nucleic acid related compounds. 84. Synthesis of 6'-(E and Z)-halohomovinyl derivatives of adenosine, inactivation of S-adenosyl-L-homocysteine hydrolase, and correlation of anticancer and antiviral potencies with enzyme inhibition.
Treatment of 9-[6-(E)-(tributylstannyl)-5,6-dideoxy-2,3-O-isopropylidene- beta-D-ribo-hex-5-enofuranosyl]adenine [2b(E)] or the 6-N-benzoyl derivative 2a(E) with iodine (or N-iodosuccinimide) or bromine (or N-bromosuccinimide) gave virtually quantitative and stereospecific conversions to the 6'-(E)-(halohomovinyl)nucleoside analogues. Analogous treatment of the 6'-(Z)-vinyl-stannanes gave the 6'-(Z)-halo compounds. Treatment of 2a or 2b with chlorine or xenon difluoride/silver triflate gave E and Z mixtures of the respective 6'-chloro- or 6'-fluorohomovinyl products. Deprotection gave the 9-[6-(E and Z)-halo-5,6-dideoxy-beta-D-ribo- hex-5-enofuranosyl]-adenines [(E and Z)-5',6'-didehydro-6'-deoxy-6'-halohomoadenosines, EDDHHAs and ZDDHHAs, 4c-7c(E and Z)]. The acetylenic 5',5',6',6'-tetradehydro-6'- deoxyhomoadenosine (3c) and the 5'-bromo-5'-deoxy-5'-methyleneadenosine (10c) regioisomer of EDDBHA [5c(E)] also were obtained from 2. Concentration- and time-dependent inactivations of S-adenosyl-L-homocysteine (AdoHcy) hydrolase were observed with 3c and the 6'-(halohomovinyl)adenosine analogues. The order of inhibitory potency was I > Br > Cl > F and E > Z for the geometric isomers. AdoHcy hydrolase effected "hydrolysis" of the 6'-halogen from the (halohomovinyl)Ado compounds (to give the putative 6'-carboxaldehyde which underwent spontaneous decomposition) independently of its oxidative activity. Partition ratios for these hydrolytic turnovers/lethal inhibitory events were in the order F > Cl > Br > I. Biological activities were evaluated with several viruses and cancer cell lines, and potencies were generally in the order I > Br > Cl > F and E > Z isomers. This represents the first observation of a direct correlation of cytostatic activity with inhibition of AdoHcy hydrolase and highlights the potential of this enzyme as a viable target for chemotherapeutic intervention in anticancer as well as antiviral drug design.


Safety and efficacy of N-acetylcysteine in hospitalized patients with HIV-associated tuberculosis: An open-label, randomized, phase II trial (RIPENACTB Study).
Despite the availability of effective antimicrobials, tuberculosis (TB) is still a serious health threat. Mortality is even higher in people living with HIV who are diagnosed with TB. New therapies are needed to shorten the time required to cure TB and decrease fatality rates in this population. N-acetylcysteine (NAC) is a glutathione precursor and has shown recently in experimental setting to present in vitro and in vivo anti-mycobacterial activity. We test the hypothesis that NAC is safe, well tolerated and secondarily efficacious as adjunctive anti-TB therapy in hospitalized individuals with HIV-associated TB. Patients were enrolled sequentially in a tertiary care center, in the Brazilian Amazon. We performed a randomized, parallel group, single-center, open study trial of two arms, in hospitalized patients over 18 years of age, with microbiologically confirmed pulmonary TB in HIV: one with rifampicin, isoniazid, pyrazinamide and ethambutol at standard doses (Control Group), and a second in which NAC 600 mg bid for eight weeks was added (NAC Group). A total of 21 and 18 patients were enrolled to the Control Group and NAC Group, respectively. Adverse event rates were similar in the two arms. Our findings suggest that in the more critical population of hospitalized patients with HIV-associated TB, the use of NAC was not unsafe, despite the low sample size, and a potential impact on faster negative cultures needs to be further explored in larger studies.


Validation of the baseline severity stratification of objective functional impairment in lumbar degenerative disc disease.
OBJECTIVE The Timed Up and Go (TUG) test is a simple, objective, and standardized method to measure objective functional impairment (OFI) in patients with lumbar degenerative disc disease (DDD). The objective of the current work was to validate the OFI baseline severity stratification (BSS; with levels of "none," "mild," "moderate," and "severe"). METHODS Data were collected in a prospective IRB-approved 2-center study. Patients were assessed with a comprehensive panel of scales for measuring pain (visual analog scale [VAS] for back and leg pain), functional impairment (Roland-Morris Disability Index [RMDI] and Oswestry Disability Index [ODI]), and health-related quality of life (HRQOL; EQ-5D and SF-12). OFI BSS was determined using age- and sex-adjusted cutoff values. RESULTS A total of 375 consecutive patients scheduled for lumbar spine surgery were included. Each 1-step increase on the OFI BSS corresponded to an increase of 0.53 in the back pain VAS score, 0.69 in the leg pain VAS score, 1.81 points in the RMDI, and 5.93 points in the ODI, as well as to a decrease in HRQOL of -0.073 in the EQ-5D, -1.99 in the SF-12 physical component summary (PCS), and -1.62 in the SF-12 mental component summary (MCS; all p < 0.001). Patients with mild, moderate, and severe OFI had increased leg pain by 0.90 (p = 0.044), 1.54 (p < 0.001), and 1.94 (p < 0.001); increased ODI by 7.99 (p = 0.004), 12.64 (p < 0.001), and 17.13 (p < 0.001); and decreased SF-12 PCS by -2.57 (p = 0.049), -3.63 (p = 0.003), and -6.23 (p < 0.001), respectively. CONCLUSIONS The OFI BSS is a valid measure of functional impairment for use in daily clinical practice. The presence of OFI indicates the presence of significant functional impairment on subjective outcome measures.


Efficient coding and the neural representation of value.
To survive in a dynamic environment, an organism must be able to effectively learn, store, and recall the expected benefits and costs of potential actions. The nature of the valuation and decision processes is thus of fundamental interest to researchers at the intersection of psychology, neuroscience, and economics. Although normative theories of choice have outlined the theoretical structure of these valuations, recent experiments have begun to reveal how value is instantiated in the activity of neurons and neural circuits. Here, we review the various forms of value coding that have been observed in different brain systems and examine the implications of these value representations for both neural circuits and behavior. In particular, we focus on emerging evidence that value coding in a number of brain areas is context dependent, varying as a function of both the current choice set and previously experienced values. Similar contextual modulation occurs widely in the sensory system, and efficient coding principles derived in the sensory domain suggest a new framework for understanding the neural coding of value.


Sustained viral suppression and higher CD4+ T-cell count reduces the risk of persistent cervical high-risk human papillomavirus infection in HIV-positive women.
Studies analyzing the impact of combination antiretroviral therapy (cART) on cervical infection with high-risk human papillomavirus (HR-HPV) have generated conflicting results. We assessed the long-term impact of cART on persistent cervical HR-HPV infection in a very large cohort of 652 women who underwent follow-up of HIV infection for a median duration of 104 months. Prospective cohort of HIV-infected women undergoing HIV infection follow-up who had HR-HPV screening and cytology by Papanicolaou smear performed yearly between 2002 and 2011. At baseline, the median age was 38 years, the race/ethnic origin was sub-Sarahan Africa for 84%, the median CD4(+) T-cell count was 426 cells/µL, 79% were receiving cART, and the HR-HPV prevalence was 43%. The median interval of having had an HIV load of <50 copies/mL was 40.6 months at the time of a HR-HPV-negative test result, compared with 17 months at the time of a HR-HPV-positive test result (P < .0001, by univariate analysis). The median interval of having had a CD4(+) T-cell count of >500 cells/µL was 18.4 months at the time of a HR-HPV-negative test result, compared with 4.45 months at the time of a HR-HPV-positive test result (P < .0001). In multivariate analysis, having had an HIV load of <50 copies/mL for >40 months (odds ratio [OR], 0.81; 95% confidence interval [CI], .76-.86; P < .0001) and having had a CD4(+) T-cell count of >500 cells/µL for >18 months (OR, 0.88; 95% CI, .82-.94; P = .0002) were associated with a significantly decreased risk of HR-HPV infection. Sustained HIV suppression for >40 months and a sustained CD4(+) T-cell count of >500 cells/µL for >18 months are independently and significantly associated with a decreased risk of persistent cervical HR-HPV infection.


Four primary tumors of lung, bladder, prostate, and breast in a male patient.
We present a very rare case of quadruple cancers in a 65-year-old male patient. It is a case of both synchronous and metachronous primary malignant neoplasms occurring in four different organs. Immunohistochemical stains showed tumor cell nuclei to be negative for p53 over-expression. To our knowledge, this is the first documented case with this combination of primary tumors. The tumors included an adenosquamous cell carcinoma of the lung, transitional cell carcinoma of the urinary bladder, and adenocarcinomas of the prostate and the breast. We also review the medical literature for the possible causes of multiple primary malignant neoplasms.


Complications and risk factors of early-onset versus late-onset gestational diabetes mellitus: A cohort study from Saudi Arabia.
To contribute to this discussion by comparing the complications associated with early-diagnosed versus (vs.) late-diagnosed gestational diabetes mellitus (GDM) for mothers and infants in order to provide baseline data that might guide future changes in the current recommendations for screening. The study compares the risk factors and complications for early- vs. late-diagnosed GDM in a cohort from Saudi Arabia. Prenatal, perinatal, postpartum, and neonatal variables were compared between the early vs. late-diagnosed GDM groups using information gathered from the patient's hospital records. Significant predictors of early-diagnosed GDM included pregestational BMI and GDM history. Additionally, early diagnosis of GDM was linked to a higher incidence of pre-eclampsia and intrauterine fetal death. Women with early-diagnosed GDM also required more glycemic control interventions, like administering insulin and metformin and controlling their diet. The fetal birth weight and postpartum BMI were significantly higher in the early onset GDM group. The need for insulin and pre-eclampsia were significant factors linked to an early diagnosis of GDM, according to a logistic regression analysis. Therefore, the current findings emphasize the need for early screening in pregnant women with high pregestational BMI and a history of GDM and show that those with early-onset GDM more likely to need insulin therapy and be at a higher risk of developing pre-eclampsia.


[Pulmonary arterial hypertension and BMP system abnormality].
Genetic analysis has uncovered that familial and idiopathic pulmonary arterial hypertension (PAH) is linked to germline mutations in BMP type II receptor (BMPRII). PAH is characterized by enhanced remodeling of pulmonary arteries due to arterial smooth muscle cell proliferation. BMPRII mutations contribute to abnormal mitotic responses to BMP ligands in pulmonary artery smooth muscle cells. Unbalanced Smad signaling induced by BMP and TGFbeta is functionally involved in the pathogenesis of PAH. BMPRII mutations also increase the susceptibility of endothelial cell apoptosis. The combination of increased endothelial injury and impaired suppression of smooth muscle cell proliferation is critical for the cellular pathogenesis of PAH. However, the detailed molecular mechanism leading to severe vascular remodeling caused by BMPRII mutations has yet to be elucidated.


Homeolog expression analysis in an allotriploid non-model crop via integration of transcriptomics and proteomics.
The fate of doubled genes, from allopolyploid or autopolyploid origin, is controlled at multiple levels, resulting in the modern day cultivars. We studied the root growth of 3 different triploid banana cultivars under control and osmotic stress conditions. The root growth of the allopolyploid ABB cultivar was 42% higher under control and 61% higher under osmotic stress. By integrating transcriptomics and proteomics, we studied the gene expression of all 3 cultivars, resulting in 2,749 identified root proteins. 383 gene loci displayed genotype specific differential expression whereof 252 showed at least one Single Amino Acid Polymorphism (SAAP). In the ABB cultivar, allele expressions supposedly follow a 1/3 and 2/3 pattern for respectively the A and the B allele. Using transcriptome read alignment to assess the homeoallelic contribution we found that 63% of the allele specific genes deviated from this expectation. 32 gene loci even did not express the A allele. The identified ABB allele- specific proteins correlate well with the observed growth phenotype as they are enriched in energy related functions such as ATP metabolic processes, nicotinamide nucleotide metabolic processes, and glycolysis.


New checkpoints in cancer immunotherapy.
Immune responses must be fine-tuned to allow effective clearance of invading pathogens, while maintain tolerance to self-antigens. T cells are the major effector cells for fighting and killing tumor cells. Immune checkpoints play a pivotal role in T cell activation, and determine the functional outcome of T cell receptor (TCR) signaling. The blockade of immune checkpoints CTLA-4 and PD-1 has already been one of the most successful cancer immunotherapies. In this review, we will focus on three novel inhibitory B7 family checkpoint molecules, B7-H3, B7S1 and VISTA. The aim of this article is to summarize their expressions in tumors as well as their roles in controlling and suppressing T cell immune responses and anti-tumor immunity. These pathways may be explored in future cancer immunotherapy.


Improving the Performance of Zn-Air Batteries with N-Doped Electroexfoliated Graphene.
The constantly growing demand for active, durable, and low-cost electrocatalysts usable in energy storage devices, such as supercapacitors or electrodes in metal-air batteries, has triggered the rapid development of heteroatom-doped carbon materials, which would, among other things, exhibit high catalytic activity in the oxygen reduction reaction (ORR). In this article, a method of synthesizing nitrogen-doped graphene is proposed. Few-layered graphene sheets (FL-graphene) were prepared by electrochemical exfoliation of commercial graphite in a Na2SO4 electrolyte with added calcium carbonate as a separator of newly-exfoliated FL-graphene sheets. Exfoliated FL-graphene was impregnated with a suspension of green algae used as a nitrogen carrier. Impregnated FL-graphene was carbonized at a high temperature under the flow of nitrogen. The N-doped FL-graphene was characterized through instrumental methods: high-resolution transmission electron microscopy, X-ray photoelectron spectroscopy, and Raman spectroscopy. Electrochemical performance was determined using cyclic voltamperometry and linear sweep voltamperometry to check catalytic activity in ORR. The N-doped electroexfoliated FL-graphene obeyed the four-electron transfer pathways, leading us to further test these materials as electrode components in rechargeable zinc-air batteries. The obtained results for Zn-air batteries are very important for future development of industry, because the proposed graphene electrode materials do not contain any heavy and noble metals in their composition.


The interaction of plasma proteins with polymers. I. Relationship between polymer surface energy and protein adsorption/desorption.
Adsorption of bovine albumin, gamma-globulin and fibrinogen from phosphate buffer solution (pH = 7.5) onto several polymer films was studied using the radioiodinated proteins (125I). The kinetics of desorption of the proteinated polymer films in bovine plasma was determined. Contact angle measurements on these same polymers allowed the calculation of dispersive (WA d) and polar (Ip) components of the polymer-protein solution system. Results from these measurements show that the nondispersive-dispersive force balance at the polymer-protein solution interface, expressed by the Ip/WA d ratio, is an important factor for binding of proteins on polymer surfaces. The purity of fibrinogen and the cleaning procedures for the polymer surfaces influence the absolute values of proteins adsorbed on polymer surfaces.


Changes in Health Expectancy for Older Adults in Japan: Results from Two Longitudinal Surveys.
Although there is evidence of improvements in health expectancy among the Japanese population, existing estimates are based on the prevalence of morbidity taken from cross-sectional survey data. This study employed a multistate life table approach to compute incidence-based health expectancy measures, namely active and inactive life expectancy (LE), for two longitudinal survey cohorts from 1990 to 2009. This study used data from two longitudinal surveys of older adults in Japan: the National Survey of the Japanese Elderly (1990-1999) and the Nihon University Japanese Longitudinal Study of Aging (1999-2009). We employed the Interpolation of Markov Chains technique to compute the number of years at age 65 years to be spent with and without difficulty in performing activities of daily living (ADLs) or instrumental ADLs. We documented significant increases in active LE for men and women at age 65 years over the 10-year study period. There were significant changes in total LE for men and in the percentage of active life for women. Inactive LE did not significantly change across the two survey cohorts during the study period. Our results show that the health status of older adults in Japan has largely improved over the 10-year study period, with increases in both the duration of life and time spent in an active state. This finding offers evidence of compression of morbidity among older men and women in Japan.


Direct Operando Observation of Double Layer Charging and Early Solid Electrolyte Interphase Formation in Li-Ion Battery Electrolytes.
The solid electrolyte interphase (SEI) is the most critical yet least understood component to guarantee stable and safe operation of a Li-ion cell. Herein, the early stages of SEI formation in a typical LiPF6 and organic carbonate-based Li-ion electrolyte are explored by operando surface-enhanced Raman spectroscopy, on-line electrochemical mass spectrometry, and electrochemical quartz crystal microbalance. The electric double layer is directly observed to charge as Li+ solvated by ethylene carbonate (EC) progressively accumulates at the negatively charged electrode surface. Further negative polarization triggers SEI formation, as evidenced by H2 evolution and electrode mass deposition. Electrolyte impurities, HF and H2O, are reduced early and contribute in a multistep (electro)chemical process to an inorganic SEI layer rich in LiF and Li2CO3. This study is a model example of how a combination of highly surface-sensitive operando characterization techniques offers a step forward to understand interfacial phenomena in Li-ion batteries.


[Current directions in professional training of surgeon].
To develop 'Cadaveric Course' of operative surgery for severe combined trauma for students, surgical residents, postgraduate students of medical universities and to compare its effectiveness with other approaches. 'Cadaveric course' program of operative surgery for severe combined trauma consisted of four stages. The first stage is theoretical course (2 weeks), the second stage - students' work in cadaveric operating theatre with instructors (5 weeks), the third stage - their independent work in 'cadaveric operating theatre (10 weeks), the fourth stage - analysis of the results and their comparison with those of 5 2-year residents (control group). There were significant differences in practical skills between students. Mean time of surgery and expert assessment score were 32.0±9.5 min and 4.6±0.5 in the main group, respectively, in the control group - 46.0±7.5 min and 3.6±0.5 scores, respectively (p=0.03 and p=0.02). Theoretical background was similar in both groups (p>0.05). Research has opened new opportunities to introduce 'cadaveric course' into educational process, to analyze its outcomes and further improvement.


Direct regulation of rRNA transcription by fibroblast growth factor 2.
Fibroblast growth factor 2 (FGF-2), which is highly expressed in developing tissues and malignant cells, regulates cell growth, differentiation, and migration. Five isoforms (18 to approximately 34 kDa) of FGF-2 are derived from alternative initiation codons of a single mRNA. The 18-kDa FGF-2 isoform is released from cells by a nonclassical secretory pathway and regulates gene expression by binding to cell surface receptors. This isoform also localizes to the nucleolus, raising the possibility that it may directly regulate ribosome biogenesis, a rate-limiting process in cell growth. Although several growth factors have been shown to accumulate in the nucleolus, their function and mechanism of action remain unclear. Here we show that 18-kDa FGF-2 interacts with upstream binding factor (UBF), an architectural transcription factor essential for rRNA transcription. The maximal activation of rRNA transcription in vitro by 18-kDa FGF-2 requires UBF. The 18-kDa FGF-2 localizes to rRNA genes and is necessary for the full activation of pre-rRNA synthesis in vivo. Our results demonstrate that 18-kDa FGF-2 directly regulates rRNA transcription.


From recollisions to the knee: a road map for double ionization in intense laser fields.
We examine the nature and statistical properties of electron-electron collisions in the recollision process in a strong laser field. The separation of the double ionization yield into sequential and nonsequential components leads to a bell-shaped curve for the nonsequential probability and a monotonically rising one for the sequential process. We identify key features of the nonsequential process and connect our findings in a simplified model which reproduces the knee shape for the probability of double ionization with laser intensity and associated trends.


Ivy1 is a negative regulator of Gtr-dependent TORC1 activation.
The highly conserved TORC1 complex controls cell growth in response to nutrients, especially amino acids. The EGO complex activates TORC1 in response to glutamine and leucine. Here, we demonstrate that the I-BAR domain-containing protein Ivy1 colocalizes with Gtr1 and Gtr2, a heterodimer of small GTPases that are part of the EGO complex. Ivy1 is a negative regulator of Gtr-induced TORC1 activation, and is contained within puncta associated with the vacuolar membrane in cells grown in nutrient-rich medium or after brief nitrogen starvation. Addition of glutamine to nitrogen-starved cells leads to dissipation of Ivy1 puncta and redistribution of Ivy1 throughout the vacuolar membrane. Continued stimulation with glutamine results in concentration of Ivy1 within vacuolar membrane invaginations and its spatial separation from the EGO complex components Gtr1 and Gtr2. Disruption of vacuolar membrane invagination is associated with persistent mislocalization of Ivy1 across the vacuolar membrane and inhibition of TORC1 activity. Together, our findings illustrate a novel negative-feedback pathway that is exerted by Ivy1 on Gtr-dependent TORC1 signaling and provide insight into a potential molecular mechanism underlying TORC1 activation by vacuolar membrane remodeling.


Mifepristone-exposured human endometrial endothelial cells in vitro.
The antiprogestin mifepristone has been used for more than 20 years as a medical alternative for early pregnancy termination. After mifepristone administration, significant changes have been observed in the endometrial vessels, with cell injury and cell death in capillary endothelial cells. In this study, the effect of mifepristone on human endometrial endothelial cells (HEECs) in vitro was evaluated using proliferation and viability assays, quantitative polymerase chain reaction of markers important for the regulation of angiogenesis, and by tube formation assay. There were no detectable effects of mifepristone on HEECs messenger RNA expression of the studied markers. Exposure to mifepristone did not alter tube formation. However, mifepristone exposure to HEECs cocultured with endometrial stromal cells significantly reduced the activity in the tube formation assay compared with mifepristone exposure of HEECs in monoculture. This implies that mifepristone causes changes in HEEC-associated angiogenic activity and that this effect is mediated through stromal cells via paracrine mechanisms.


Memory in naturalistic and laboratory contexts: distinguishing the accuracy-oriented and quantity-oriented approaches to memory assessment.
A distinction is drawn between the quantity-oriented approach to memory that has dominated traditional laboratory research, and the accuracy-oriented approach that is emerging in the study of everyday memory. This distinction is shown to underlie some troubling confusions in the interpretation of empirical findings. In particular, the recall-recognition paradox, which involves the claimed superiority of recall over recognition memory in naturalistic settings, is shown to stem from the common confounding between memory property (quantity vs. accuracy) and 2 other variables that have not generally been distinguished--test format (production vs. selection) and report option (free vs. forced reporting). Three laboratory experiments reveal the fundamentally different roles played by report option and test format in accuracy-based and quantity-based memory research. Implications for memory assessment, metamemory, and the everyday-laboratory controversy are discussed.


Fronto-parietal networks shape human conscious report through attention gain and reorienting.
How do attention and consciousness interact in the human brain? Rival theories of consciousness disagree on the role of fronto-parietal attentional networks in conscious perception. We recorded neural activity from 727 intracerebral contacts in 13 epileptic patients, while they detected near-threshold targets preceded by attentional cues. Clustering revealed three neural patterns: first, attention-enhanced conscious report accompanied sustained right-hemisphere fronto-temporal activity in networks connected by the superior longitudinal fasciculus (SLF) II-III, and late accumulation of activity (>300 ms post-target) in bilateral dorso-prefrontal and right-hemisphere orbitofrontal cortex (SLF I-III). Second, attentional reorienting affected conscious report through early, sustained activity in a right-hemisphere network (SLF III). Third, conscious report accompanied left-hemisphere dorsolateral-prefrontal activity. Task modeling with recurrent neural networks revealed multiple clusters matching the identified brain clusters, elucidating the causal relationship between clusters in conscious perception of near-threshold targets. Thus, distinct, hemisphere-asymmetric fronto-parietal networks support attentional gain and reorienting in shaping human conscious experience.


Antagonism by beta-adrenoceptor blocking agents of the antianaphylactic effect of isoprenaline.
1. beta-Adrenoceptor blocking agents antagonized the inhibitory (antianaphylactic) effect of isoprenaline on antigen-induced histamine release in isolated, passively sensitized, human lung and actively sensitized guinea-pig lung suggesting that the effect is exerted through beta-adrenoceptors. No antagonism was obtained with the human allergic leucocyte preparation.2. The antianaphylactic effect of isoprenaline was antagonized not only by propranolol but also by the ;selective' beta-adrenoceptor blocking agents, practolol and butoxamine.3. The classification of beta-adrenoceptors is discussed. Certain similarities between antianaphylactic and lipolytic beta-adrenoceptors are noted.


Changes in the ascertainment of multiple sclerosis.
With diagnostic criteria alterations, increased MRI availability, and awareness of therapies, temporal changes in incidence and prevalence rates may occur, with an increase in the proportion of mildly affected persons diagnosed with multiple sclerosis (MS). The authors assessed temporal trends in the delay from symptom onset to diagnosis (DONDX), and determined whether the degree of disability at diagnosis differs by year of symptom onset (YONSET), using the NARCOMS Registry. The authors selected US participants with an age at symptom onset of 10 to 60 years, and YONSET > or = 1980 (n = 16,581). The authors divided YONSET into 5-year groups and compared DONDX between groups using multivariate Cox regression. The authors classified participants enrolled within 2 years of diagnosis (n = 5,548) as having mild, moderate, or severe disability using Patient Determined Disease Steps, and assessed the association of disability with YONSET using polytomous logistic regression. DONDX decreased with later YONSET (r = -0.43, p < 0.0001). This association remained after adjustment for demographic factors in a multivariate Cox model. Later YONSET was associated with increased odds of having mild disability at diagnosis as compared to severe disability (OR = 1.10 per year; 1.09 to 1.11). The delay from symptom onset to diagnosis is steadily decreasing in MS. An increasing proportion of patients with MS have mild disability at diagnosis after accounting for confounders. As the effectiveness of therapies is influenced by disease duration, this has implications for comparison of treatment effects in modern clinical trials to earlier study results.


Correlation between salivary cortisol levels and dental anxiety in children of smokers and nonsmokers.
The present study was undertaken to evaluate salivary cortisol levels in children of smokers and nonsmokers and thereby establishing the relationship between cortisol levels in response to anxiety in children based on their father's habit of smoking. The study population aged between 8 and 10 years includes two groups. Group 1 is comprised 20 children of cigarette smokers and Group 2 is comprised 20 children of nonsmokers. The passive drooling technique was used to collect unstimulated saliva from the children using a sterile container. Salivary cortisol levels were evaluated using Enzyme-linked Immunosorbent Assay method. The obtained data were subjected to statistical analysis using SPSS software and paired t-test. Higher mean salivary cortisol levels were found in children of smokers compared to children of nonsmokers and the difference between them was significant statistically (P < 0.05). Higher salivary cortisol levels were found in females compared to males and the result was significant statistically (P < 0.05). This study has proved that the smoking habit of the father has a negative influence on the anxiety levels of their children.


Epirubicin and docetaxel as neoadjuvant treatment of hormone receptor positive, HER-2 negative breast cancer: findings from two successive phase II studies.
We report on the activity of the combination of epirubicin and docetaxel given in neoadjuvant setting for 4 and 8 cycles respectively in 2 successive series of patients with large operable or locally advanced, hormone receptor positive, HER-2 negative breast cancer. Patients were treated from 2002 to 2006 with epirubicin 90 mg/m(2) and docetaxel 75 mg/m(2) intravenously, every 3 weeks for 4 cycles before and 4 cycles after surgery (Series I - 13 patients), and from 2006 to 2010 with the same regimen administered for 8 cycles preoperatively (Series II - 37 patients), plus hormonal therapy for 5 years and radiation therapy if indicated. All Series I and 32 Series II patients were able to complete the preoperative chemotherapy. A complete response was found in 1 patient from Series I and 13 patients from Series II and the partial remission in 10 patients from Series I and 21 patients from Series II. Two Series I and 3 Series II patients did not respond clinically. Response rate (Series I/Series II) was 84/92%. All 50 patients underwent surgery. In Series I patients, 3 pCR occurred in the breast and the axilla was histologically negative in 2 cases. No evidence of disease both in the breast and in the axilla was achieved in 7.6% (1/13) of patients. In Series II patients, 8 pCR occurred in the breast and axilla was histologically negative in 15 patients. No evidence of disease both in the breast and in the axilla occurred in 10.8% (4/37) of patients. G3-G4 toxicity included myelosuppression in 3 patients from Series I and all patients from Series II, and mucositis in 1 patient from Series I and 4 patients from series II. No other G3-4 toxicities or toxic deaths occurred. Five-year progression free survival was 38% and 90% in Series I and Series II patients respectively. The incidence of pathologic complete remissions was lower in our patient population, compared to reported data. A longer duration of the preoperative treatment might be associated with a longer progression-free survival.


Optimizing a Thomson scattering diagnostic for fast dynamics and high background.
The Madison Symmetric Torus (MST) presents challenging conditions for Thomson scattering (TS) measurements. The MST plasmas are reversed-field pinches (RFPs) with electron density n(e)<3x10(13) cm(-3), typically 1x10(13) cm(-3). The TS system was designed to measure from 10 eV to 2 keV; however, six polychromators were upgraded from four to eight spectral channels to resolve to 10 keV. There is no diverter or vertical field, so wall interaction results in high background light both from ion and neutral bremsstrahlungs and from line radiation. Also during standard plasmas, the RFP exhibits regular reconnection sawteeth events during which the plasma current, density, and temperature profiles are flattened. These events are of interest both due to the reconnection physics and to their contribution to the MST equilibrium and confinement. These events occur over 100 microS and exhibit large changes in background light and fast changes in temperature. During improved confinement plasmas, there are no sawteeth; the background is low but the temperature can be over an order of magnitude higher. Data analysis of the system has been developed to accommodate both the large dynamic range of the temperature, the fast dynamics, and the fast changing, high amplitude background. Special attention has been paid to the sources of error, in particular, the contribution of the background. A response-function method reduces the measured uncertainty by a factor of 2. Numerical techniques have been developed which are extremely robust. Two methods are used, a conventional chi(2) minimization using a Levenberg-Marquardt algorithm coupled with Monte Carlo modeling for the error bar and a Bayesian statistics method. The Bayesian method computes the probability distribution for the measured photons and electron temperature and this information can be used to ensemble data and will allow future integrated data analysis efforts.


Regulatory Aspects of Human Milk Oligosaccharides.
Human milk oligosaccharides are key components of human milk and appear in various compositions and concentrations in all human milks. In regulatory sense human milk oligosaccharides are classified as novel foods or novel food ingredients requiring safety assessment. In addition, if any health messages are intended to be used also health claim regulations apply. This chapter reviews the regulatory settings and studies human milk oligosaccharides are required to fulfill to be able to enter markets in European Union or United States or elsewhere. Examples include Lacto-N-neotetraose and 2-fucosyllactose with safety assessment in European Union and United States.


Clinicopathologic characteristics of ovarian clear cell carcinoma in the background of endometrioma: a surveillance strategy for an early detection of malignant transformation in patients with asymptomatic endometrioma.
This study aimed to analyze the clinical features of clear cell carcinoma in relation to endometriosis and to determine an appropriate surveillance strategy for the early detection of malignant transformation of endometrioma in asymptomatic patients. We retrospectively reviewed the clinicopathologic data of 50 patients with ovarian clear cell carcinoma. Clinicopathologic characteristics, treatment outcomes, and the association between endometriosis and the risk of malignant transformation were analyzed. Ten (20%) patients had been diagnosed with endometrioma before the diagnosis of clear cell carcinoma. The median period from the diagnosis of endometrioma to clear cell carcinoma diagnosis was 50 months (range, 12-213 months). After complete staging surgery, histological confirmation of endometriosis was possible in 35 (70%) patients. Of the 50 patients, 39 (78%) had not undergone any gynecologic surveillance until the onset of symptoms, at which time many of them presented with a rapidly growing pelvic mass (median 10 cm, range 4.6-25 cm). With the exception of 2 patients, all cancer diagnoses were made when the patients were in their late thirties, and median tumor size was found to increase along with age. Asymptomatic patients (n=11) who had regular gynecologic examinations were found to have a relatively smaller tumor size, lesser extent of tumor spread, and lower recurrence rate (P=0.011, 0.283, and 0.064, respectively). The presence of endometriosis was not related to the prognosis. Considering the duration of malignant transformation and the timing of cancer diagnosis, active surveillance might be considered from the age of the mid-thirties, with at least a 1-year interval, in patients with asymptomatic endometrioma.